第二代环氧酶-2特异性抑制剂的研究进展

为降低NSAIDs类药物的典型胃肠道不良反应，人们开发了选择性更高的第二代环氧酶-2(COX-2)特异性抑制剂。已开发的代表性化合物有戊地昔布、帕瑞昔布、依地昔布和氯美昔布等。临床试验证实，这些药物具有可靠的抗炎和止痛作用，其中帕瑞昔布作为第一个注射用NSAIDs类药物，可用于治疗手术后疼痛。本文综述该领域的研究进展。     

塞来昔布的药理作用、药代动力学及临床评价

目的:评价特异性环氧酶抑制剂——塞来昔布的药理作用、药代动力学及临床疗效。方法:评述国内、外近期有关塞来昔布的文献。结果:推荐剂量的塞来昔布治疗骨关节炎和风湿性关节炎疗效与传统的非甾体抗炎药物(NSAIDs)相似,疗效确切,但较少引起胃肠道溃疡,且不延长出血时间,耐受性良好。结论:塞来昔布与目前国内、外广泛应用的NSAIDs相比,疗效确切,降低了胃肠道损伤的发生率,与治疗高血压、糖尿病等药物联用,没有明显的药物相互作用。     

常用药物引起的胃肠道不良反应及预防

在临床常用药物引起的不良反应中,胃肠道发病率较高,其并发症可威胁人的生命。因此积极开展用药监测,预防不良反应的发生尤为重要。本篇即对常用药物引起的胃肠道不良反应的发病机制和临床特点进行分析,并对预防胃肠道不良反应的发生提出了相应对策。     

常用药物引起的胃肠道不良反应及预防

为了解可引起胃肠道不良反应的常用药物,经检索有关文献资料,对各类药物可能引起胃肠道不良反应的发病机制和临床特点进行分析。结果药物致胃肠道不良反应发病率较高,其并发症可威胁人的生命。因此,应积极开展用药监测,预防药物致胃肠道不良反应的发生,尽可能减轻患者病痛。     

1例抗结核药致胃肠道不良反应的药学监护

目的探讨临床药师参与结核患者胃肠道不良反应处理的方法与思路。方法临床药师查阅相关指南及文献,协助医生制定抗结核药致胃肠道不良反应的处理方案。结果药学服务取得了明显临床疗效,患者胃肠道不良反应明显改善,且未对抗结核治疗的疗效产生不利影响。结论临床药师应积极发挥专业优势,在药物治疗过程中早期发现并鉴别药物不良反应,积极寻找不良反应解决方案。     

药源性胃肠道不良反应

目的 本文探讨药物引起的胃肠道不良反应。方法 时临床用药多数产生不良反应的患者，进行引起胃肠道疾病原因的分析。结果 药源性胃肠道不良反应后果严重．应引起临床用药的高度重视。     

浅谈影响药物经胃肠道吸收的因素

影响药物经胃肠道吸收的因素很多,药物理化性质、给药途径、吸收过程中的解剖学、生理学、病理学和药物剂型以及首过代谢等各种因素均可影响.本文就主要影响药物经胃肠道吸收的因素进行讨论,旨在为临床合理用药提供参考.     

静滴红霉素所致胃肠道反应的药物防治

目的介绍静滴红霉素所致胃肠道反应的药物防治．为临床用药提供参考。方法查阅有关文献资料,结合临床实际,进行分析和归纳。结果用口服笮脱石、静滴山莨菪碱、口服硝苯地平等方法来防治静滴红霉素所致的胃肠道反应。均可收到良好的效果。结论红霉素具有广泛的临床用途。但伴随而来的恶心、呕吐、腹痛、暖泻等胃肠道不良反应也不容忽视。用蒙脱石、山莨萤碱、硝苯地平等药物防治红霉素的胃肠道反应。经济实用。效果良好．并可提高病人对用药的依从性,值得临床大力推广。     

抗痨药物的胃肠道损害

目的总结抗痨药物在治疗结核病过程中引发的胃肠道损害及其处理对策。方法回顾性分析我院收治的128例肺结核患者的临床资料。结果临床上出现的胃肠道损害主要类型有:腹泻、便秘、急性胃炎、慢性胃炎、消化性溃疡、肠易激综合征;利福平、吡嗪酰胺以及左氧氟沙星引起胃肠道损害的人次较多。结论使用抗痨药物治疗结核病的过程中应密切注意患者的身体状况,对胃肠道损害以及其他不良反应尽早采取应对办法。     

腹腔温热灌注联合全身化疗治疗胃肠道恶性肿瘤的护理体会

胃肠道恶性肿瘤是临床上常见的消化道恶性肿瘤。目前。对于中晚期胃肠道肿瘤病人临床上多采用全身化疗．但疗效并不满意。因此如何降低胃肠道恶性肿瘤术后复发和转移发生率．提高病人的长期生存率已成为目前临床研究的热点之一。近年来，腹腔温热灌注化疗凭借温热条件下的局部药物浓度高、化疗药物敏感性强、全身毒性低的优势，逐步应用于临床。     

选择性环氧化酶2抑制剂的不良反应

选择性环氧化酶2(COX-2)抑制剂是治疗类风湿关节炎和骨关节炎的一类新型非甾体抗炎药(NSAIDs)。选择性COX-2抑制剂分为倾向性COX-2抑制剂(美洛昔康、尼美舒利和双氯芬酸等)和特异性COX-2抑制剂(塞来昔布、罗非昔布、伐地考昔、依托考昔等),前者对COX-2的抑制作用明显大于对COX-1的抑制作用,但在抑制COX-2的同时也会部分抑制COX-1,后者仅对COX-2有强烈抑制作用。选择性COX-2抑制剂的主要不良反应为消化道溃疡、穿孔或出血,肾功能损伤,凝血功能障碍,以及血栓形成等。其机制与选择性COX-2抑制剂能同时抑制COX-1和COX-2,减弱其对消化道黏膜的保护作用、使肾小球滤过率下降而加重钠钾潴留、抑制细胞色素P4502C9酶活性而降低华法林代谢率以及影响血栓素A2和前列腺素I2的平衡等有关。同时服用选择性COX-2抑制剂与质子泵抑制剂可降低消化道不良反应的发生率;高血压病患者或有水钠潴留倾向者服用选择性COX-2抑制剂时,应定期监测血药浓度及肾功能,调整降压药剂量,避免多种NSAIDs同时应用;选择性COX-2抑制剂与小剂量阿司匹林联合应用可防治心血管不良反应。一旦出现不良反应,应立即停药并对症治疗。     

Profiles of COX-2 inhibitors: present and future

Cyclooxygenases are responsible for the biosynthesis of prostanoids, the overt presence of which is often associated with inflammation and pain. Since the discovery of COX-2 in the last decade, a myriad of selective COX-2 inhibitors and their pharmacological profiles have been witnessed. Pharmacological observations of selective inhibition of COX-2 often go beyond initial expectations. This review is an overview of issues on selective COX-2 inhibitors, which include gastrointestinal and cardiovascular safety, emerging therapeutic areas and differentiation in drug profiles expected to be addressed by future generation COX-2 inhibitors. This article also covers recent patents and papers on new COX-2 inhibitors published since 2002. Future generation COX-2 inhibitors are sure to be safer and meet better medical needs than the COX-2 inhibitors currently available for the treatment or prevention of broadly ranged COX-2-mediated disorders.     

COX-2抑制剂联合抗肿瘤的研究进展

环氧酶-2(cyclooxygenase 2,COX-2)抑制剂具有预防和治疗多种肿瘤的作用,并且能够影响化疗药物的抗肿瘤活性。COX-2抑制剂联合化疗药物抗肿瘤可能成为肿瘤治疗的新方法。该文对国内外COX-2抑制剂联合化疗药物抗肿瘤的临床前和临床研究进行综述,分析研究结论中存在的争议,并探讨影响化疗效果的可能机制。     

Cyclooxygenase 2 selective inhibitors in cancer treatment and prevention

Prostaglandin synthesis by a number of enzymes is important at all stages during the genesis of cancer. The availability of prostaglandin H(2) as a substrate for prostaglandin production is a critical control point in its synthesis. Cyclooxygenase (COX) occurs in two forms (COX-1 and -2) and acts as the rate-limiting enzyme that generates prostaglandin H(2). COX-1 is produced as a steady-state enzyme, while COX-2 is heavily involved in inflammation and tumorigenesis. Differences in the catalytic sites of these enzymes are utilised to generate COX-2 selective inhibitors. Certain chemical characteristics of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors make some of these inhibitors more effective against COX-2 than others. Epidemiological, animal and preclinical data demonstrate the promise of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors as anticancer agents. Ongoing clinical trials are designed to determine the efficacy of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors in the prevention and treatment of many types of cancer.     

Novel insights and therapeutical applications in the field of inhibitors of COX-2

The discovery of the two isoenzymes COX-1 and COX-2 and the knowledge of their function, localisation and regulation has initiated the development of COX-2 selective inhibitors (coxibs). Inducible COX-2 at the peripheral site of inflammation has been detected in the early 1990s, the involvement of recently detected spinal COX-2 has led to new insights into mechanisms of pain and may explain analgesic and antipyretic properties of COX-2 selective inhibitors. The coxibs rofecoxib and celecoxib have been introduced into therapy and seem to offer some advantages over the classical non-selective NSAIDs. The search for new COX-2 inhibitors is going on, the development of etoricoxib and lumiracoxib is a step ahead concerning efficacy, tolerability and safety. Until today COX-2 selective inhibitors have found their place in therapy of arthritis, osteoarthritis, dysmenorrhea and acute pain. A new paradigm in pain therapy seems to justify their use in perioperative settings in a preemptive or multimodal therapeutical strategy. In the future COX-2 selective inhibitors as opioid sparing agents could become an important tool in pain therapy. Even a therapeutical benefit of COX-2 selective inhibitors in the treatment of Alzheimer's Disease or in the prevention or treatment of colorectal or prostate cancer is presently intensely investigated. Recently some authors reported on COX-3, a splicing variant of COX-1. If COX-3 really represents the target for acetaminophen must be called into question.     

The second generation of COX-2 inhibitors: what advantages do the newest offer?

The discovery of two cyclooxygenase (COX)-isoenzymes, a constitutive COX-1, serving homeostatic prostanoid synthesis, and an inducible COX-2, responsible for proinflammatory prostanoid production, led to the development of new non-steroidal anti-inflammatory drugs (NSAIDs), the selective COX-2 inhibitors, promising minimal NSAID-typical toxicity with full anti-inflammatory efficacy. So far, the strategy of selective COX-2 inhibition has been successful. Selective COX-2 inhibitors have significantly less gastrotoxicity and no effects on platelet aggregation. However, with regard to renal adverse events, selective COX-2 inhibitors do not offer a clinically relevant advantage over non-selective inhibitors. Moreover, concerns over the cardiovascular risk of selective COX-2 inhibitors have recently been raised. The second generation of COX-2 inhibitors with higher COX-2 selectivity was developed with the promise of further reduction of NSAID-typical adverse effects. The leading compounds are valdecoxib, parecoxib, etoricoxib and lumaricoxib. At the present time they have proven efficacy for the treatment of pain and inflammation. Parecoxib as a parenteral, highly selective COX-2 inhibitor has the potential to become the NSAID of choice for treatment of postoperative pain. In clinical trials, valdecoxib, parecoxib, etoricoxib and lumaricoxib have caused no more endoscopic ulcers than placebo. However, to date, no data on the clinically relevant endpoints perforation, symptomatic ulcer and bleeding are available. Furthermore, no definite conclusions on renal and cardiovascular safety are possible. Current evidence points to a marginal, if any, gain of safety compared with the first generation of COX-2 inhibitors. However, trials with the new COX-2 inhibitors offer the chance to address these open questions of highly selective COX-2 inhibition; that is, thrombogenic risk, sodium and water retention, and interference with tissue repair, in particular, healing of mucosal damage.     

选择性 COX-2抑制剂引发心血管事件研究进展

通过对国内外选择性环氧化酶-2(COX-2)抑制剂致心血管事件的相关文献检索.分析和总结了此类药物引发心血管事件的毒理学、相关研究和药害事件.提示在使用 COX-2抑制剂时,应关注其心血管等方面存在的潜在风险,采用短期低剂量治疗方法,同时对患者心血管方面的生命体征进行定期监测.     

Efficacy of the newest COX-2 selective inhibitors in rheumatic disease

Non-steroidal antiinflammatory drugs (NSAIDs) are standard treatment for the pain and inflammation associated with arthritis. Traditional NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors exhibit comparable efficacy, with different safety profiles. Traditional NSAIDs are associated with an increased risk of serious gastrointestinal (GI) adverse events versus COX-2 selective inhibitors, and chronic use frequently necessitates adjunctive therapy with gastroprotective agents. COX-2 selective inhibitors are often used in preference to avoid these GI adverse events. Recent studies have raised the concern that COX-2 selective inhibitors and traditional NSAIDs appear to be associated with a higher incidence of thrombotic cardiovascular events versus placebo. The key in prescribing these agents is for the physician to take a proactive approach to patient management and evaluation of GI and cardiovascular risk factors. This review examines the role of the newest COX-2 selective inhibitors, etoricoxib and lumiracoxib, in treating rheumatic disease.     

Cyclooxygenase 2 selective inhibitors in cancer treatment and prevention

Prostaglandin synthesis by a number of enzymes is important at all stages during the genesis of cancer. The availability of prostaglandin H₂ as a substrate for prostaglandin production is a critical control point in its synthesis. Cyclooxygenase (COX) occurs in two forms (COX-1 and -2) and acts as the rate-limiting enzyme that generates prostaglandin H₂. COX-1 is produced as a steady-state enzyme, while COX-2 is heavily involved in inflammation and tumorigenesis. Differences in the catalytic sites of these enzymes are utilised to generate COX-2 selective inhibitors. Certain chemical characteristics of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors make some of these inhibitors more effective against COX-2 than others. Epidemiological, animal and preclinical data demonstrate the promise of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors as anticancer agents. Ongoing clinical trials are designed to determine the efficacy of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors in the prevention and treatment of many types of cancer.     

Cyclooxygenase-2 inhibitors: a literature and patent review (2009 - 2010)

INTRODUCTION: COXs catalyze the complex conversion of arachidonic acid to prostaglandins and thromboxanes, which trigger as autacoids with autocrine and paracrine biological effects many physiological and pathophysiological responses. The structural similarities of the COX-1 and -2 enzymes make the search for selective inhibitors for COX-2 versus -1 a formidable challenge. AREAS COVERED: The present review provides a survey of the development of novel COX-2 inhibitors covering literature and patents between 2009 and 2010. The presence of a central, typically 1,2-diaryl substituted, heterocycle or carbocycle as a characteristic structural motif in many selective COX-2 inhibitors represents the basis of their classification in this review. The classification in this review includes COX-2 inhibitors based on five- and six-membered heterocycles, benzoheterocycles (e.g., benzopyrans, benzopyranones, indoles and quinolines), quinones, chalcones, natural products and miscellaneous. When available, COX-2 inhibitors are presented with their related COX-2 inhibitory potency and selectivity. EXPERT OPINION: The availability of detailed information on the crystal structure of the COX-2 enzyme with various substrates, cofactors and inhibitors, and the recently reported increased risk of cardiovascular events associated with selective COX-2 inhibitors will further stimulate development of COX-2 inhibitors with favorable COX-2 inhibition profiles without adverse effects to the cardiovascular system.